Quote:CCR5 bound by leronlimab would have no immune capability since it binds to the CCR5's n-terminus blocking CCL cytokines from binding. But that slack would be taken up by the other CCR receptors allowing immune functionality.
Early work showed that PA14/PRO140 blocked HIV entry but still allowed CCL5 to work at low doses. It is only at high doses that LL/PA14/PRO140 blocks CCL5 and other chemokines from binding and activating the CCR5 receptor. Cytodyn used to (falsely) claim that LL would block HIV but still allow checmokines and the immune system to function "normally," as if that were a good thing.
See Figure 3 here:
https://journals.asm.org/doi/full/10.1128/jvi...-4155.1999
Quote:Whereas 2D7 and RANTES binding maps primarily to ECL2, the PA14 epitope maps to both ECL2 and the Nt domain and may have less potential for steric overlap. These data demonstrate the feasibility of developing chemokine receptor-specific HIV-1 inhibitors that do not block normal receptor activity, an observation with considerable therapeutic implications.
Now to say the complete opposite (that LL completely blocks CCL5 and CCL2 binding to CCR5 so it has no immune capability) may not be completely true. Maybe it's a question of dosing or semantics in what you are saying.
Agree with you that LL blocks "normal" immune system to some extent by blocking CCL5 and CCL2 from binding to CCR5, but only at higher doses.
The interesting thing is that we *want* to block CCL5 and CCL2 from binding to CCR5 in cancer and anti-inflammatory / immune dampening indications. Cytodyn had it all wrong for years by claiming that it didn't do this. 2D7 antibody was much better at blocking CCL2/RANTES activation at lower doses (8 fold lower) than PA14/LL in these early studies.
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